Herpes simplex virus 2 (HSV-2) causes genital herpes and increases the risk of transmission and infection with HIV. Thus a vaccine for HSV-2 would not only reduce the rate of genital herpes, but also might reduce spread of HIV. Several HSV-2 vaccines have been tested in humans for prevention or reduction of genital herpes disease, but none has been licensed for use in humans. We completed a clinical trial of a replication-defective vaccine for HSV-2 termed HSV529. This vaccine can infect cells, but not replicate in the cells. We vaccinated three groups of 20 subjects with HSV529 (15 subjects per group) or saline placebo injection (5 subjects per group). The groups were a) subjects who were infected with HSV-2 in the past but may or may not have been infected with HSV-1 (HSV-1+/-/HSV-2+), (b) subjects who were infected only with HSV-1 (HSV-1+/HSV-2-), and (c) subjects who were not infected with HSV-1 or HSV-2 (HSV-1-/HSV-2-). Each subject was followed after vaccination and safety and immune responses to the vaccine were studied. The data from the study are currently being evaluated.